The proposed study is aimed at elucidating the mechanism of action of insecticides on the nervous system. Special emphasis is placed on the interactions of insecticides with sodium and potassium channels of nerve membranes and on the structure-activity relationship based on the measurement of direct action of the target site, the nervous system. The specific project for the coming year involves the voltage clamp analysis of pyrethroid-sodium channel interactions using squid and crayfish giant axons. Kinetic analysis will be performed to determine the nature of changes in channel function caused by pyrethroids in the nerve membrane, the antagonisms between pyrethroids and other neuroactive toxins and drugs whose sites of action are well defined will be investigated. Furthermore, the interaction between the active and inactive isomers of pyrethroids will be studied in an attempt to determine the stereospecificity of these compounds. The results of the proposed study will be of immense importance in understanding the molecular mechanism of insecticide action on the nerve.